The project is concerned with the metabolism and morphology of tissues that are sites of diabetic complications, and possible pathogenetic mechanisms. The metabolism and morphology of a newly developed aortic intima-media preparation which retains an intact endothelium will be examined; evidence that incubation with elevated glucose concentrations induces significant alterations in the structure of the endothelium and in the composite metabolism of the tissue will be sought to confirm preliminary observations. The metabolism of free myoinositol in the tissue will be studied, and the possible relationship of alterations in its metabolism and the effects of exposure to anoxia and high glucose concentrations on endothelial cell structure and composite tissue metabolism examined. A newly developed isolated sciatic nerve fascicle preparation will be employed to study the effects of insulin, hyperglycemia, and experimental diabetes on the energy, glucose, and myoinositol metabolism of this tissue. Collaborative studies to delineate the possible ultrastructural alterations in peripheral nerve myelin associated with impaired nerve conduction velocity in acute experimental diabetes will be continued. BIBLIOGRAPHIC REFERENCES: Morrison, A.D., Berwick, L., Orci, L., and Winegrad, A.I. Morphology and metabolism of an aortic intima-media preparation in which an intact endothelium is preserved. J. Clin. Invest. 57: 650-660, 1976. Winegrad, A.I., and Clements, R.S., Jr. Demonstrable metabolic abnormalities in diabetes mellitus that may contribute to the pathogenesis of specific late complications. In: Diabetes Mellitus, Stefan S. Fajans, editor, Fogarty International Center Series on Preventive Medicine, National Institutes of Health, Bethesda, Maryland, Vol. 4, pps. 173-193, 1976.